Saturday, June 9, 2012

Recombinant Human Activated Protein C in Sepsis


Bahar Mjos, DO

 

Evaluating the use of recombinant human activated protein C in adult severe sepsis: Results of the Surviving Sepsis Campaign*

Casserly, Brian MD; Gerlach, Herwig MD, PhD; Phillips, Gary S. MAS; Marshall, John C. MD; Lemeshow, Stanley PhD; Levy, Mitchell M. MD

After the PROWESS-SHOCK trial and Cochrane review in 2012, it appeared that the controversy related to efficacy of activated protein C and its role in sever sepsis had been resolved. However, this month in the journal of Critical Care Medicine, revisited this topic.

It has been shown that after adjusting for multiple confounders, patients who received rhAPC had statistically significantly lower in-hospital mortality. “Propensity score matching was used to validate the risk adjusted multivariate regression model, and the results were similar. Patients with thrombocytopenia and coagulopathy also were found to have lower, and statistically significant, adjusted risks of hospital mortality”.

As of October 2011 Xigris (activated protein C) has been withdrawn from the market.
“While further discussions about rhAPC might be considered moot, it is worth noting that previous rigorously conducted clinical trials occasionally have yielded discordant results compared to observational, “real-life” investigations. The recent moratorium on the use of rhAPC appears to represent yet another failure of immunomodulatory agents to impact outcomes for critically ill patients with sepsis; however, the infrequent use of rhAPC, in selected populations, was found to be associated with a significant improvement in adjusted hospital mortality in this study.”

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